Funding is requested for a cryogenically-cooled, ultra high-sensitivity triple resonance, 1H{13C/15N}, 5 mm probe and associated closed-cycle cryogenic system for an existing modern Varian Inova 600 MHz NMR spectrometer at Brandeis University. The cryoprobe technology has been demonstrated to provide a significant improvement in signal-to noise ratios for studies of biologically important macromolecules. The 600 MHz spectrometer is currently heavily used for high-resolution, high-sensitivity multidimensional NMR experiments, typically with isotopically labeled (15N, 13C, 2H) biological samples in solution. The cryoprobe/cryoplatform will significantly increase the sensitivity and throughput of the instrument. Three investigators from Brandeis University along with two scientists from Tufts University and Boston University constitute the initial major users of the cryoprobe. The increase in sensitivity gained by the cryoprobe will allow the research groups to perform experiments that are currently not practical on the existing spectrometer. Technically demanding projects such as studies of the dynamics and structure of (i) enzymes during catalysis, (ii) shortly-lived macromolecular species and (iii) large proteins and protein/protein complexes for which only low concentrated samples can be reached will greatly benefit from the increase in signal-to noise ratio. Finally, the increased throughput of the system will accelerate the NIH supported research projects since NMR time is currently one limiting factor. The technical skills are available to maintain and operate the instrument at the NMR facility at Brandeis.